Developing a drug, from early candidate molecule discovery up to placing the product on the market, is a long and costly process, involving significant human and equipment investment. Notably, clinical trials which involve human tests could take several years. The aim of these trials is to ensure the efficiency of the drug, highlight potential side effects and evaluate safety concerns of the therapeutics.
Upstream of these clinical trials, the preclinical trials have great importance. It is during this preclinical development that the candidate molecule is identified, selected and validated. Preclinical development specifically uses animal trials to study the pharmacology of the candidate molecule. Particularly, the purpose of these pharmacological studies is to validate in-vitro and in-vivo the mechanism of action and measure the activity of the candidate molecule in animal disease models. Moreover, they provide an evaluation of the candidate molecule's behavior and its potential transformation in a living organism and help to establish its target organs or tissue and the toxicity doses for the model.
Clinical trial relevance is consequently related to the upstream of preclinical studies during which large numbers of molecules, interesting at first sight, are finally discarded. Preclinical studies must permit a reliable selection, from dozens of candidate molecules, of the most promising one which can be an active ingredient in a drug formulation for the treatment of a given pathology. Poor preclinical evaluation may lead to the selection of a candidate molecule that will demonstrate its inefficiency in clinical phases, causing losses in terms of time and cost.
Therefore, it is important to have reliable investigations to evaluate whether a candidate molecule acts on the right target, especially on a given tissue, does not involve side effects, and is not blocked by a biological barrier. For example, numerous molecules identified in vitro as potential active compounds for central nervous system (CNS) disease treatment are unable, during in vivo trials, to cross the blood-brain barrier and thus are totally ineffective.
Today, more than 35% of candidate molecules discarded in clinical trials have been wrongly selected in preclinical phases following incorrect evaluation of their action in the target tissue.
For that reason, there is a real need for reliable methods of candidate molecule selection to ensure its high binding specificity for a given target tissue, allowing the accurate evaluation of its pharmacokinetics within this tissue. There is also a need in the case of phytosanitary product development to have more data about potential toxicity or lack of toxicity of the product on the living organism by using a method to evaluate whether a candidate molecule binds or is incorporated in at least one target tissue.